rs770919315

Variant names:

• chr4-112514892-C-A
• rs770919315
• NM_024019.4:c.584G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-112514892-C-A
• chr4-112514892-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024019.4(NEUROG2):​c.584G>T​(p.Gly195Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,624 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G195A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: NEUROG2 NM_024019.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.53
• Publications: 0 publications found

Genes affected

NEUROG2 (HGNC:13805): (neurogenin 2) This gene encodes a neural-specific basic helix-loop-helix (bHLH) transcription factor that can specify a neuronal fate on ectodermal cells and is expressed in neural progenitor cells within the developing central and peripheral nervous systems. The protein product of this gene also plays a role in the differentiation and survival of midbrain dopaminergic neurons. [provided by RefSeq, Apr 2012]

NEUROG2-AS1 (HGNC:40656): (NEUROG2 and ZGRF1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024019.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEUROG2	NM_024019.4	MANE Select	c.584G>T	p.Gly195Val	missense	Exon 2 of 2	NP_076924.1	Q9H2A3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEUROG2	ENST00000313341.4	TSL:1 MANE Select	c.584G>T	p.Gly195Val	missense	Exon 2 of 2	ENSP00000317333.3	Q9H2A3
	NEUROG2-AS1	ENST00000754767.1		n.53C>A		non_coding_transcript_exon	Exon 1 of 5
	NEUROG2-AS1	ENST00000754768.1		n.47C>A		non_coding_transcript_exon	Exon 1 of 6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449624 Hom.: 0 Cov.: 34 AF XY: 0.00000139 AC XY: 1 AN XY: 720480

African (AFR) AF: 0.00 AC: 0 AN: 33134

American (AMR) AF: 0.00 AC: 0 AN: 42360

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25752

East Asian (EAS) AF: 0.00 AC: 0 AN: 39412

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 85086

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50936

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5102

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108046

Other (OTH) AF: 0.00 AC: 0 AN: 59796

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.45	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.093	N
LIST_S2	Benign	0.60	T
M_CAP	Pathogenic	0.51	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Uncertain	0.29	D
MutationAssessor	Benign	0.0	N
PhyloP100		3.5
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.62	N
REVEL	Uncertain	0.38
Sift	Benign	0.049	D
Sift4G	Benign	0.11	T
Polyphen		0.98	D
Vest4		0.46
MutPred		0.20		Loss of disorder (P = 0.0566)
MVP		0.98
MPC		1.9
ClinPred		0.67	D
GERP RS		3.7
Varity_R		0.20
gMVP		0.64
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs770919315; hg19: chr4-113436048;